[Ectopic tissue of the female genital tract]. / Ektopes Gewebe des weiblichen Genitaltraktes.

Ectopias of female genital tissues are a common event in routine pathology. Mostly they derive from paramesonephric tissues displaced during embryonal development or later. However, gonadal-, mesonephric-, or mesothelial-derived tissues may also appear in unusual localizations in and outside the female genital tract. They may be the source of benign and malignant tumors or tumor-like lesions. This review aims to provide an overview of possible tissue ectopias and to improve the developmental understanding of tumorous diseases of the female genital tract. Ectopias of primarily extragenital tissues in the female genital tract are also reviewed.

Whole-body FDG PET/CT is more accurate than conventional imaging for staging primary breast cancer patients.

PURPOSE: This retrospective study aimed (1) to compare the diagnostic accuracy of whole-body FDG PET/CT for initial breast cancer staging with the accuracy of a conventional, multimodal imaging algorithm, and (2) to assess potential alteration in patient management based on the FDG PET/CT findings. METHODS: Patients with primary breast cancer (106 women, mean age 57 ± 13 years) underwent whole-body FDG PET/CT and conventional imaging (X-ray mammography, MR mammography, chest plain radiography, bone scintigraphy and breast, axillary and liver ultrasonography). The diagnostic accuracies of FDG PET/CT and a conventional algorithm were compared. Diagnostic accuracy was assessed in terms of primary tumour detection rate, correct assessment of primary lesion focality, T stage and the detection rates for lymph node and distant metastases. Histopathology, imaging or clinical follow-up served as the standards of reference. RESULTS: FDG PET/CT was significantly more accurate for detecting axillary lymph node and distant metastases (p = 0.0125 and p < 0.005, respectively). No significant differences were detected for other parameters. Synchronous tumours or locoregional extraaxillary lymph node or distant metastases were detected in 14 patients (13%) solely by FDG PET/CT. Management of 15 patients (14%) was altered based on the FDG PET/CT findings, including 3 patients with axillary lymph node metastases, 5 patients with extraaxillary lymph node metastases, 4 patients with distant metastases and 3 patients with synchronous malignancies. CONCLUSION: Full-dose, intravenous contrast-enhanced FDG PET/CT was more accurate than conventional imaging for initial breast cancer staging due to the higher detection rate of metastases and synchronous tumours, although the study had several limitations including a retrospective design, a possible selection bias and a relevant false-positive rate for the detection of axillary lymph node metastases. FDG PET/CT resulted in a change of treatment in a substantial proportion of patients.

Diagnostic accuracy of fused positron emission tomography/magnetic resonance mammography: initial results.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of fused fluoro-deoxy-D-glucose positron emission tomography/magnetic resonance mammography (FDG-PET/MRM) in breast cancer patients and to compare FDG-PET/MRM with MRM. METHODS: 27 breast cancer patients (mean age 58.9±9.9 years) underwent MRM and prone FDG-PET. Images were fused software-based to FDG-PET/MRM images. Histopathology served as the reference standard to define the following parameters for both MRM and FDG-PET/MRM: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the detection of breast cancer lesions. Furthermore, the number of patients with correctly determined lesion focality was assessed. Differences between both modalities were assessed by McNemars test (p<0.05). The number of patients in whom FDG-PET/MRM would have changed the surgical approach was determined. RESULTS: 58 breast lesions were evaluated. The sensitivity, specificity, PPV, NPV and accuracy were 93%, 60%, 87%, 75% and 85% for MRM, respectively. For FDG-PET/MRM they were 88%, 73%, 90%, 69% and 92%, respectively. FDG-PET/MRM was as accurate for lesion detection (p = 1) and determination of the lesions' focality (p = 0.7722) as MRM. In only 1 patient FDG-PET/MRM would have changed the surgical treatment. CONCLUSION: FDG-PET/MRM is as accurate as MRM for the evaluation of local breast cancer. FDG-PET/MRM defines the tumours' focality as accurately as MRM and may have an impact on the surgical treatment in only a small portion of patients. Based on these results, FDG-PET/MRM cannot be recommended as an adjunct or alternative to MRM.

[Intraocular medulloepithelioma - series of 10 cases and review of the literature]. / Intraokulare Medulloepitheliome - klinische Serie mit 10 Fällen.

Intraocular medulloepithelioma is an extremely rare unilateral intraocular tumor arising from the nonpigmented ciliary epithelium. Medulloepitheliomas may be classified as benign and malignant and as teratoid and nonteratoid tumors. As a rule a long latency period occurs after first symptoms until the final diagnosis of a medulloepithelioma is made. Differential diagnosis includes in particular unilateral retinoblastoma. Intraocular medulloepithelioma may occur as masquerade-syndrome simulating uveitis. We present 10 patients with intraocular medulloepithelioma. In 7 of these patients the eye had to be enucleated. Metastasis did not occur, but epiretinal tumor seeding did occur in one patient. In one of the 3 not enucleated eyes, ruthenium-106 brachytherapy could salvage the tumor containing eye.

[Aquaporin 1 expression in invasive breast carcinomas]. / Aquaporin-1-Expression bei invasiven Mammakarzinomen.

Aquaporin1 (AQP1) is a water channel protein which facilitates water flux across cell membranes. AQP1 is found in epithelial and endothelial cells in various tissues. There is increasing evidence that AQP1 is expressed in malignant tumours and that it may play a role in tumour angiogenesis, cell migration and metastasis. We studied the immunohistochemical expression of AQP1 in a cohort of 203 invasive breast carcinomas with long-term follow up. AQP1 expression was detected in 11 cases (5.4%), and showed a significant correlation with high tumour grade, medullary-like histology, "triple-negativity", as well a cytokeratin 14 and actin expression. In univariate analysis, AQP1 was associated with a significantly poorer prognosis. Multivariate analysis showed that AQP1 expression has an independent predictive value for outcome if stratified by age, tumour size, lymph node status, histological grade and ER status. AQP1 expression in invasive breast carcinomas is associated with a basal-like phenotype and poor prognosis.

MR-guided vacuum-assisted breast biopsy with a handheld biopsy system: clinical experience and results in postinterventional MR mammography after 24 h.

This prospective study evaluates the feasibility of the magnetic resonance (MR)-guided vacuum-assisted breast biopsy with a handheld vacuum-biopsy system and documents the biopsy results with MR mammography 24 h after the procedure. MR-guided biopsy was undertaken in 33 patients with 34 lesions on dynamic MR mammography. The interventions were performed with the handheld 10-gauge Vacora vacuum-biopsy system. In all cases, dynamic MR mammography was performed 24 h after the procedure to determine the extent of the lesion removal and to identify the lesions that were missed. In 5/34 (14.7%) lesions, biopsy was not performed because no suspicious lesion was identified on the day of biopsy. In 25/29 (86.2%) lesions, the biopsy was successfully performed with a complete removal in 4/29 (13.8%) and a partial removal of 21/29 (72.4%) lesions. In 4/29 (13.8%) interventions the lesion was missed with the biopsy. In one case, histopathology after surgical excision revealed ductal carcinoma in situ. Histopathology revealed 9/29 (31%) malignant and 20/29 (68.9%) benign lesions. MR-guided vacuum-assisted breast biopsy with the handheld Vacora vacuum-biopsy system is technically feasible in most cases. MR mammography 24 h after the biopsy should be performed in those cases in which the biopsy success is unclear immediately after the procedure.

[Salivary gland-like tumors of the breast]. / Tumoren vom Speicheldrüsentyp in der Mamma.

A subset of rare benign and malignant breast tumors with and without myoepithelial differentiation are morphologically and histogenetically similar to salivary gland tumors, but may differ in incidence and clinical behavior. The clinicopathological, immunohistochemical, molecular and prognostic features of ten salivary gland-like tumor entities of the breast are discussed and compared with their respective counterparts in the salivary glands.

Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways.

BACKGROUND AND AIM: The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways-namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu-is assessed in a series of 113 node-negative breast cancers. RESULTS: COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis. CONCLUSIONS: The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed-COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.

Relationship and prognostic significance of phospho-(serine 166)-murine double minute 2 and Akt activation in node-negative breast cancer with regard to p53 expression.

The Akt signalling pathway plays a central role in tumourigenesis. Activation of Akt is related to a more aggressive phenotype in various human cancers, including breast cancer. Its activation contributes to cancer progression via pleiotropic effects, including suppression of apoptosis and modulation of cell cycle regulation. Murine double minute 2 (MDM2) is an oncoprotein that inhibits the function of p53 tumour suppressor protein. Cell culture studies show that Akt-related phosphorylation of MDM2 at serine 166 allows MDM2 to gain nuclear entry and fulfil its p53 regulating function. This study was designed to analyse the relationship of phospho-MDM2 (pMDM2) expression with Akt activation to determine a possible prognostic relevance of pMDM2 in node-negative breast cancer with respect to Akt activation and p53 status. pMDM2, phospho-Akt (pAkt) and p53 protein expression status were analysed immunohistochemically in 121 paraffin-embedded breast cancer cases. Expression of pMDM2 correlated with Akt activation (P<0.001). Univariate analysis identified pMDM2 as a prognostic factor (P=0.0458) in node-negative breast cancers. The unfavourable prognostic significance was even more pronounced in tumours with a pMDM2(+)/pAkt(+) immunophenotype (P=0.0205). Stratification into a p53-negative subgroup further strengthened the adverse prognostic influence. These data confirm that MDM2 phosphorylation at serine 166 is mediated by Akt kinase. Besides the prognostic impact of pMDM2, our findings suggest that Akt-mediated modulation of the MDM2/p53 complex contributes to increased tumour aggressiveness especially in p53-negative breast cancers. However, due to the relatively small number of patients in this cohort, the results obtained need to be confirmed by larger cohorts.

[MR-guided vacuum assisted breast biopsy]. / Die Magnetresonanztomographie(MRT)-gesteuerte Mamma-Vakuumbiopsie mit dem Vacora-System -- Erste Ergebnisse.

OBJECTIVE: This prospective study was undertaken to determine the feasibility of MR-guided vacuum assisted breast biopsy with the Vacora-vacuum-biopsy system for histological evaluation of suspicious lesions in MR-mammography. MATERIAL AND METHODS: During 3 months MR-guided vacuum assisted breast biopsy was indicated in 12 patients with suspicious lesions in MR-mammography. RESULTS: MR-guided vacuum assisted breast biopsy with the Vacora-vacuum-biopsy system could be performed in 9 of 12 patients. In 2 patients the lesions could not be identified at the time of the intervention. In one patient the intervention could not be performed due to obesity. Histopathology revealed benign lesions in 8 patients and malignancy in one patient. In one of the cases with benign histology, the biopsy specimen was not representative for the lesion. CONCLUSIONS: MR-guided vacuum assisted breast biopsy with Vacora-vacuum-biopsy is technical feasible can be performed with a low complication rate.

ETV6-NTRK3 gene fusion in a secretory carcinoma of the breast of a male-to-female transsexual.

Secretory carcinomas of the breast were first described as "juvenile carcinoma" by McDivitt and Stewart in a cohort of children. This term has been replaced by the term "secretory breast carcinoma", because the entity can occur at any time of life. Carcinoma of the male breast is uncommon and accounts for approximately 1% of all cancers in men. Recently, it has been reported that human secretory breast carcinoma expresses the ETV6-NTRK3 gene fusion that was previously cloned in pediatric mesenchymal cancers. We present the case of a 46-year-old male-to-female transsexual in whom a secretory breast carcinoma was an incidental finding. As confirmation of the histopathological diagnosis we detected the novel ETV6-NTRK3 gene fusion in this tumor.

Prognostic value of c-erbB-2 expression in papillary thyroid carcinoma.

AIMS: c-erbB-2 overexpression has been shown to be a potential marker of aggressive biological behaviour in a varity of tumours, whereas its role played in thyroid papillary thyroid carcinoma (PTC) remains unclear. Objective of the study is to determine whether c-erbB-2 overexpression correlates with the clinical course. METHODS: We have studied 32 PTC by a two-step immunocytochemical staining procedure for paraffin-embedded specimens (DAKO Hercep-Test). Semiquantitative evaluations were performed, based on the intensity of immunostaining and the percentage of tumor cells. RESULTS: 34% (11/32) of the PTC showed a membranous overexpression of the HER2/neu oncoprotein. Correlating the pathological and clinical data revealed that 81% (9/11) c-erbB-2 positive patients and only 33% (7/21) c-erbB-2 negative patients developed a tumor recurrence or a progression (p = 0.02 in Fisher's exact test). 3/11 c-erbB-2 positive patients died from PTC whereas all (21/21) c-erbB-2 negative patients are still alive (p = 0.03). CONCLUSIONS: Our results strongly suggest that c-erbB-2 oncoprotein overexpression is related to the clinical course of PTC.

Erdheim-Chester disease: case report with multisystemic manifestations including testes, thyroid, and lymph nodes, and a review of literature.

Erdheim-Chester disease is a rare non-Langerhans' cell histiocytosis with characteristic radiological and histological features. This entity is defined by a mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain positively for CD68. About half of those affected have extraskeletal manifestations, including involvement of the hypothalamus-pituitary axis, lung, heart, retroperitoneum, skin, liver, kidneys, spleen, and orbit. This report describes the case of a 50 year old white man who presented with hypogonadism and diabetes insipidus. At necropsy, extensive organ involvement was found, including the testes, thyroid, and lymph nodes. This is the first report of thyroid and lymph node infiltration in this disease. Because of the endocrinological symptoms, neurosarcoidosis and hypophysitis are important diseases in the differential diagnosis. This report also includes a review of the literature concerning rare organ manifestations and patients presenting primarily with similar symptoms.

[Hyperplasia and tumors of the parathyroid glands]. / Hyperplasien und Tumoren der Nebenschilddrüsen.

Hyperparathyroidism is mainly caused by hyperplasia or adenomas of the parathyroid glands. Formerly, the therapeutic strategy depended on the morphological diagnosis (preferentially already made intraoperatively by examination of frozen sections). Today, however, the extent of parathyroid surgery is in many cases guided both by substantial improvements in the preoperative clinical diagnosis as well as the intraoperatively determined decrease in the serum parathyroid hormone level. Nevertheless, the pathologist should be familiar with the differential diagnostic criteria of parathyroid hyperplasia, adenoma, and carcinoma.

[Purpura fulminans. A fatal consequence of a widely used medication?]. / Purpura fulminans Fatale Folge einer alltäglichen Therapie?

A 39-year old man developed purpura fulminans, a manifestation of disseminated intravascular coagulopathy, with rhabdomyolsis following the i.m. injection of diclofenac.

Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast.

AIMS: This study was performed to determine the diagnostic value of keratin 5/6 (CK 5/6) immunophenotyping on routinely processed breast tissues. METHODS AND RESULTS: Six hundred and ninety-nine breast lesions, including normal tissues as well as benign and malignant lesions in 321 formalin-fixed, paraffin-embedded samples from 158 different patients were investigated immunohistochemically, following wet autoclave pre-treatment for antigen retrieval. In normal breast tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in varying amounts. While myoepithelial immunoreactivity was most pronounced in the duct system, luminal epithelial immunoreactivity was strongest in the terminal duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an expression, whereas in ductal in-situ carcinomas (DCIS) and in infiltrating ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive immunostaining for CK 5/6. CONCLUSIONS: Immunophenotyping of keratin 5/6 expression can be helpful in the diagnosis of atypical hyperplasias and in-situ carcinomas of the breast. It is particularly valuable in the differential diagnosis between benign and atypical proliferative lesions.

Comparative genomic hybridization of ductal carcinoma in situ of the breast-evidence of multiple genetic pathways.

There is strong evidence that ductal carcinoma in situ (DCIS) represents a precursor lesion of invasive breast cancer. In order to analyse specific chromosomal alterations of DCIS, 38 paraffin-embedded specimens of DCIS and six associated invasive carcinomas were examined by means of comparative genomic hybridization (CGH). Losses of 16q material were seen almost exclusively in well- and intermediately-differentiated DCIS. These two subgroups differed in the average number of genetic imbalances, 2.5 and 5.5 respectively. Additionally, a higher frequency of gains of 1q and losses of 11q material was seen in intermediately-differentiated in contrast to well-differentiated DCIS. Poorly-differentiated DCIS displayed a higher frequency of amplifications (17q12, 11q13) and a higher average rate of genetic imbalances (7.1). Analysis of adjacent invasive breast carcinoma revealed a genetic pattern almost identical to the one seen in the DCIS counterpart. These data characterize DCIS as a genetically far-advanced, heterogeneous lesion and as a direct precursor of invasive breast cancer.

Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes.

Invasive breast cancer shows a wide range of morphological differentiation, associated with differences in prognosis, but as yet, the underlying genetic mechanisms cannot be accounted for. In order to establish a model of the possible progression from the different subtypes of ductal carcinoma in situ (DCIS) to invasive breast cancer, 77 selected cases of invasive breast cancer representing distinct morphological subtypes were investigated by means of comparative genomic hybridization (CGH). There was a high degree of genetic homology between tubular and tubulo-lobular carcinoma and well-differentiated DCIS, and between ductal invasive carcinoma G3 and poorly differentiated DCIS. Highly differentiated invasive breast cancers were characterized by a loss of 16q and a low average number of aberrations per case. In high-grade tumours, losses of this chromosomal region were seen with a much lower frequency in cases with evidence of an aneuploid tumour status. These data demonstrate the close genetic similarity of well-, intermediately, and poorly differentiated DCIS and distinct morphological types of invasive breast carcinoma, providing further evidence that DCIS is a direct precursor lesion of invasive breast cancer and that various evolutionary genetic pathways exist.